Role of the C2 domain in protein kinase C enzyme function

Marceen Newlon

Appointment Period: 1999-2000 / Grant Year: [15]

The goal of this project was to understand how the structure of PKC regulates its function. Specifically, this project addressed how the binding of ligands to the C1 and C2 domains results in release of the pseudosubstrate from the substrate-binding cavity. The main question to be be addressed was: what are the interfaces between the various domains of protein kinase C that allow communication between the regulatory modules and the active site? As a model system for this work, PKA was exploited due to the rich biochemistry and cell biology associated with this related kinase. This ultimately proved to be very rewarding and productive. The goal of this work was thus to understand the molecular details of how the architecture and chemistry of PKA and PKC are regulated by interactions between its domains to understand how this class of enzymes transduces cellular information.